{"title":"Effects of progestogen neurosteroids on locomotor activity in zebrafish embryos and larvae.","authors":"Mandarin Mathouchanh, Charles A Lessman","doi":"10.1007/s10695-025-01519-6","DOIUrl":null,"url":null,"abstract":"<p><p>The steroid hormone progesterone (P4) and related compounds called progestogens are well known for their effects on the reproductive system. However, their physiological roles outside reproduction are less understood. Additionally, there is limited information on the toxicological repercussions of environmental exposure to exogenous progestogens and how such exposure might impact the development and survival of animals living in contaminated habitats. Two progesterone-based neurosteroids, allopregnanolone and tetrahydrodeoxycorticosterone (THDOC), are known to enhance γ-aminobutyric acid type A (GABA<sub>A</sub>) receptor activity, inducing neuronal hyperpolarization. In this study, locomotor parameters in zebrafish embryos and larvae were used as endpoints to assess the inhibitory effects of pregnane neurosteroids. Specifically, spontaneous tail coiling in embryos at 24 h post-fertilization (hpf) and swimming activity in larvae aged 120-168 hpf were evaluated. Motility assays in embryos showed that P4 increased spontaneous tail coiling, whereas larvae exhibited an anesthetic-like loss of motility. This effect was both age- and dose-dependent for P4, deoxycorticosterone (DOC), 5α-dihydroprogesterone, and the membrane progesterone receptor agonist, ORG-OD-02-0, but not for other steroids tested. Removal of the steroids after the onset of anesthesia led to recovery of motility in larvae, suggesting that the observed effects are not due to a non-specific toxicity. Our results suggest that P4 targets the mPR, which acts in association with the GABA<sub>A</sub> receptor to mediate the loss of locomotor behavior. This study provides further insight into how neuroactive compounds can affect locomotor behaviors during early developmental stages in nonmammalian species.</p>","PeriodicalId":12274,"journal":{"name":"Fish Physiology and Biochemistry","volume":"51 3","pages":"105"},"PeriodicalIF":2.5000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122642/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fish Physiology and Biochemistry","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1007/s10695-025-01519-6","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The steroid hormone progesterone (P4) and related compounds called progestogens are well known for their effects on the reproductive system. However, their physiological roles outside reproduction are less understood. Additionally, there is limited information on the toxicological repercussions of environmental exposure to exogenous progestogens and how such exposure might impact the development and survival of animals living in contaminated habitats. Two progesterone-based neurosteroids, allopregnanolone and tetrahydrodeoxycorticosterone (THDOC), are known to enhance γ-aminobutyric acid type A (GABAA) receptor activity, inducing neuronal hyperpolarization. In this study, locomotor parameters in zebrafish embryos and larvae were used as endpoints to assess the inhibitory effects of pregnane neurosteroids. Specifically, spontaneous tail coiling in embryos at 24 h post-fertilization (hpf) and swimming activity in larvae aged 120-168 hpf were evaluated. Motility assays in embryos showed that P4 increased spontaneous tail coiling, whereas larvae exhibited an anesthetic-like loss of motility. This effect was both age- and dose-dependent for P4, deoxycorticosterone (DOC), 5α-dihydroprogesterone, and the membrane progesterone receptor agonist, ORG-OD-02-0, but not for other steroids tested. Removal of the steroids after the onset of anesthesia led to recovery of motility in larvae, suggesting that the observed effects are not due to a non-specific toxicity. Our results suggest that P4 targets the mPR, which acts in association with the GABAA receptor to mediate the loss of locomotor behavior. This study provides further insight into how neuroactive compounds can affect locomotor behaviors during early developmental stages in nonmammalian species.
期刊介绍:
Fish Physiology and Biochemistry is an international journal publishing original research papers in all aspects of the physiology and biochemistry of fishes. Coverage includes experimental work in such topics as biochemistry of organisms, organs, tissues and cells; structure of organs, tissues, cells and organelles related to their function; nutritional, osmotic, ionic, respiratory and excretory homeostasis; nerve and muscle physiology; endocrinology; reproductive physiology; energetics; biochemical and physiological effects of toxicants; molecular biology and biotechnology and more.